This grant application is for a New Investigator Research Award to support Dr. William Hammond for studies on the regulation of hematopoiesis in dogs and patients with cyclic hematopoiesis. In the proposed investigations in the in vitro growth characteristics of canine and human bone marrow cells will be studied in a long-term flask culture system. In the first phase of this work the long-term culture system will be developed for dog marrow cells and set up in our laboratory for human cells. Then studies will be done to see if cyclic hematopoiesis marrow cycles in vitro and if the cycling is attributable to the presence of a specific group of cells in the culture flask, eg. adherent marrow cells, non-adherent marrow cells, mature neutrophils. Subsequently studies on the effect of adding lithium carbonate and glucocorticosteroids to the cultures will be performed. The establishment of stable long-term cultures in vitro, by eliminating the high risk of infection and making the cells accessible to manipulations not possible in vivo, should permit elucidation of the roles of specific adherent cell populations, non-adherent cell concentrations and diffusable short-range regulatory factors in the pathogenesis of cycling. The extension of such studies to human tissues could than determine the applicability of these concepts in human myelopoiesis. The localization of the primary defect to a particular cell population and the definition of its mechanism of action would enhance our understanding of hematopoietic regulation and potentially reveal new therapeutic options for human cyclic hematopoiesis and related disorders.